Elasmobranch fishes (sharks, skates, and rays) are relatively disease free (Wellings, S. R., 1969, Natl. Cancer Inst. Mongr. 31:59-128), particularly with regard to the lack of cancerous tumors. As documented by the Registry of Tumors in Lower Animals maintained at the Smithsonian Institution (Harshbarger, J. C., 1965-present), a few tumors have been described from this large subclass of fish, but their incidence is acknowledged to be a rarity. Since elasmobranchs are notably resistant to tumor development, these fish have been well studied with regard to their cancer resistance. The immune system in elasmobranchs has been studied to investigate anti-tumor and cytokine-like factors present in their immune systems. Compared to other lower vertebrate animal systems, relatively little functional information is available regarding the cells and tissues which comprise the elasmobranch immune system (McKinney, E. C., 1992, Ann. Rev. of Fish Diseases 2:43-51). While elasmobranchs do not have bone marrow, they do have a thymus (Fänge, R. and Pulsford, A., 1983, Cell and Tissue Research 230:337-351; Lloyd-Evans, P., 1993, Developmental and Comparative Immunology 17:501-514; Luer, C. A., Walsh, C. J., Bodine, A. B., Wyffels, J. T., Scott, T. R., 1995, J. of Experimental Zoology 273:342-354) and a spleen, as well as two lymphomyeloid organs which are unique to this subclass of fish, the Leydig organ surrounding the esophagus, and the epigonal organ associated with the gonads. Histologically, the Leydig and epigonal organs of elasmobranchs resemble bone marrow and lymph nodes of higher vertebrates and are very active in granulopoiesis and lymphocyte production (Fänge, R. and Mattison, A., 1981, Biol. Bull. 160:240-249; Fänge, R., 1987, Arch. Biol. 98:187:208; Fänge, R., 1994, Fish and Shellfish Immunology 4(6):405:411). While many elasmobranchs possess both of these lymphoid organs, some have only the epigonal organ (Honma, Y., Okabe, K., and Chiba, A., 1984, Jap. J. Icht., 31:47-54; Fänge, 1987). Other than the role of these tissues in granulopoiesis and lymphopoiesis, little is known of the functional aspects of the cells within these unique tissues. Cells produced by the epigonal and/or Leydig organs may be important in immune responses and in inflammatory processes of elasmobranchs (Fänge and Mattisson, 1981).
Shark cartilage has been studied with regard to its anti-angiogenic properties. Lee and Langer (1983, Science 221:1185-1187) and Folkman and Klagsbrun (1987, Science 235:442-446) have shown that sharks produce a substance which inhibits neovascularization. There are several therapeutically valuable compounds isolated from sharks. For example, U.S. Pat. No. 5,192,756 discloses a compound having antibiotic and antiprotozoal properties isolated from the stomach of a dogfish shark. U.S. Pat. No. 5,075,112 describes a method for inhibiting angiogenesis using shark cartilage, and U.S. Pat. No. 5,985,839 describes extracts of shark cartilage having anti-angiogenesis properties and an inhibitory effect on cell tumor lines.
An antimitogenic factor derived from the epigonal organ of a dogfish shark was shown to reversibly inhibit DNA synthesis in spermatocysts in the testis (Piferrer, F. C., and Callard, G. V., 1995, Biology of Reproduction, 53:390-398). Previously, juvenile (total length<75 cm) nurse shark (Ginglymostoma cirratum) epigonal cells and cleamose skate (Raja eglanteria) epigonal and Leydig organ cells were placed into short-term culture (Walsh, C. J. and Luer, C. A., 1998, Fish and Shellfish Immunology, 8:197-215). These cultures included a cell culture medium that had been modified to approximate the normal osmolarity (970 mOsm) of elasmobranch cells using urea, NaCl, and trimethylamine N-oxide (TMAO) to balance the medium isotonically. Urea is a major balancing osmolyte naturally present in marine cartilaginous fish, including elasmobranch fishes. TMAO is a solute naturally concentrated in the urea-rich cells of elasmobranchs that serves to offset the damaging effects of urea on intracellular protein structure and function by raising the free energy of the denatured state of proteins, and also stabilizes the osmolyte urea. These preparations were not evaluated for anti-tumor or immunosuppressive activity. Therapeutically valuable biological activity demonstrated by a factor isolated from cultures of immune cells of elasmobranchs has not yet been described.